Scientists discover a massacre: “assassin” cells murdering innocent cells

Scientists discovered that a quarter of the progenitor cells in the testes are “murdered” by phagocytes, even though these cells are not doing anything “wrong”.

Research from the University of Haifa has identified killer cells.

A process involving the “murder” of living, newly created cells was first discovered in recent research at Haifa University. The research detailed in the prestigious journal scientific advancesdiscovered that phagocytes consume and destroy healthy living cells during the cellular differentiation process in fruit flies.

“We found that phagocytes can act as ‘killers’. It is known that phagocytes swallow and dissolve dead cells, but we show for the first time that they also kill newly formed normal cells. In essence, we have characterized a new mechanism of cell death. The more we know the mechanisms of cell death, the better we understand how we cope with various diseases, especially cancer,” explains Professor Hilla Toledano, head of the Department of Human Biology at the University of Haifa and author of the study.

The origin of several body tissues, including skin, hair, stomach and testicles, can be traced back to stem cells. By continually supplying new cells to replace the old ones, these powerful stem cells enable tissue replenishment. Each stem cell splits into two cells in this process, one of which is retained for future use and the other develops to take the place of the lost cell in the tissue.

In the current study, Professor Toledano, Professor Estee Kurant and a group of scientists from the University of Haifa examined the gametes of fruit flies. Since many molecular processes in fruit flies and humans are similar, they can be used as an effective model in this situation.

Fruit fly studies are useful because of the ability to monitor processes in living tissue and the ease of genetic modification that allows for accurate identification of cellular processes. Over the years, six Nobel Prizes have been awarded to scientists who discovered biological mechanisms in fruit flies that are conserved in humans.

As previously mentioned, the division of a stem cell into two cells – a stem cell and a cell known as a progenitor – begins the sperm differentiation process in male fruit flies. This process continues until viable sperm are formed. The researchers already knew from previous studies that a quarter of these progenitor cells die off and do not develop into sperm. The aim of the present study was to gain a better understanding of what happens to these cells.

The body has a well-established and critical mechanism called cell death. Under normal circumstances, cells have the ability to “commit suicide” when a severe mutation has occurred or after they have served their purpose. Phagocytes come to “eat” dying cells, effectively absorbing and dissolving their contents. It is known that phagocytes sometimes “eat” immune system cells that have finished their job of defending the body against invaders.

In the current study, the researchers found that the scavenger cells “kill” a quarter of the progenitor cells in the testes, although these cells are not doing anything “wrong” and are only in the process of differentiation; they are still new cells and they are not abnormal in any way.

In the first step, the researchers prevented the scavenger cells from eating and found no dead cells in the tissue. In other words, the scavenger cells are responsible for the death of the progenitor cells.

In the second step, the researchers monitored living tissue using real-time imaging and found that the progenitor cells are swallowed alive by the phagocyte and only then the death process is initiated. “For the first time, we have found a process in which normal cells are ‘killed’. We still don’t know why this is happening. Perhaps this process aims to provide nutrients to maintain a functional population of stem cells throughout the organism’s lifespan,” Professor Toledano suggested.

In addition to understanding a new mechanism, this study may contribute to our abilities to develop drugs and agents to control cell death and, of course, to treat cancer in particular. “Tumors are characterized by constant growth and the disruption of the process of natural cell death. If we succeed in introducing scavenger cells into this process that are able to eliminate the living cancer cells, we can control the growth of the tumor. The more we learn about cell death mechanisms, the better we can use these processes to get rid of cancer cells,” concluded Professor Toledano.

Reference: “The phagocytic cyst cells in Drosophila testis eliminate germ cell progenitors by phagoptosis” by Maayan Zohar-Fux, Aya Ben-Hamo-Arad, Tal Arad, Marina Volin, Boris Shklyar, Ketty Hakim-Mishnaevski, Lilach Porat-Kuperstein, and Estee Kurant Hila Toledano, June 17, 2022, scientific advances.
DOI: 10.1126/sciadv.abm4937